Reference - Detail
| RRC ID | 51835 |
|---|---|
| Author | Lin Y, Ohkawara B, Ito M, Misawa N, Miyamoto K, Takegami Y, Masuda A, Toyokuni S, Ohno K. |
| Title | Molecular hydrogen suppresses activated Wnt/β-catenin signaling. |
| Journal | Sci Rep |
| Abstract |
Molecular hydrogen (H2) is effective for many diseases. However, molecular bases of H2 have not been fully elucidated. Cumulative evidence indicates that H2 acts as a gaseous signal modulator. We found that H2 suppresses activated Wnt/β-catenin signaling by promoting phosphorylation and degradation οf β-catenin. Either complete inhibition of GSK3 or mutations at CK1- and GSK3-phosphorylation sites of β-catenin abolished the suppressive effect of H2. H2 did not increase GSK3-mediated phosphorylation of glycogen synthase, indicating that H2 has no direct effect on GSK3 itself. Knock-down of adenomatous polyposis coli (APC) or Axin1, which form the β-catenin degradation complex, minimized the suppressive effect of H2 on β-catenin accumulation. Accordingly, the effect of H2 requires CK1/GSK3-phosphorylation sites of β-catenin, as well as the β-catenin degradation complex comprised of CK1, GSK3, APC, and Axin1. We additionally found that H2 reduces the activation of Wnt/β-catenin signaling in human osteoarthritis chondrocytes. Oral intake of H2 water tended to ameliorate cartilage degradation in a surgery-induced rat osteoarthritis model through attenuating β-catenin accumulation. We first demonstrate that H2 suppresses abnormally activated Wnt/β-catenin signaling, which accounts for the protective roles of H2 in a fraction of diseases. |
| Volume | 6 |
| Pages | 31986 |
| Published | 2016-8-25 |
| DOI | 10.1038/srep31986 |
| PII | srep31986 |
| PMID | 27558955 |
| PMC | PMC5001535 |
| MeSH | Adenomatous Polyposis Coli Protein / antagonists & inhibitors Adenomatous Polyposis Coli Protein / genetics Adenomatous Polyposis Coli Protein / metabolism Animals Axin Protein / metabolism Casein Kinase I / metabolism Cell Line Chondrocytes / cytology Chondrocytes / drug effects Chondrocytes / metabolism Gases / chemistry Glycogen Synthase Kinase 3 / metabolism HCT116 Cells HT29 Cells HeLa Cells Humans Hydrogen / chemistry Hydrogen / pharmacology* Leupeptins / pharmacology Lithium Chloride / pharmacology Male Microscopy, Fluorescence Osteoarthritis / metabolism Osteoarthritis / pathology Osteoarthritis / veterinary Phosphorylation / drug effects RNA Interference RNA, Small Interfering / metabolism Rats Rats, Sprague-Dawley SOX9 Transcription Factor / metabolism Water / chemistry Wnt Signaling Pathway / drug effects* Wnt3A Protein / metabolism beta Catenin / metabolism* |
| IF | 3.998 |
| Times Cited | 9 |
| Altmetric score |
オルトメトリクス指標項目
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| The most frequently cited source | |
| Total number of mentions | 6 |
| Altmetric score changes over past 6months | 0.0 |
| Resource | |
| Human and Animal Cells | Hep G2(RCB1886) ATDC5(RCB0565) |